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A6485 - Relapsing Pulmonary Alveolar Proteinosis Treated with GM-CSF
Author Block: E. Alkhankan1, H. Alkhankan2, H. S. Bukamur1, A. Amro1, M. A. Megri3, F. Alkhankan4, F. M. Zeid1; 1Pulmonary Medicine, Marshall University, Huntington, WV, United States, 2Pulmonary and Critical Care Medicine, Mercy Hospital/St. Louis University, Saint Louis, MO, United States, 3Pulmonary Medicine, Marshall university, Huntington, WV, United States, 4Pulmonary / Critical Care Medicine, McLaren Oakland, Pontiac, MI, United States.
Introduction:
Pulmonary Alveolar Proteinosis (PAP) is rare disorder caused by a large deposition of lipoproteins in alveoli. It can be congenital, Acquired or idiopathic. We present a case of relapsing PAP was successfully treated with recombinant granulocyte macrophage-colony stimulating factor GM-CSF (Sargramostim).
Case Presentation:
A 51-year-old, non-smoking female presented with shortness of breath for several months. She was hypoxemic and on exam she had coarse inspiratory crackles bilaterally with digital clubbing. A Chest CT scan showed diffuse bilateral ground glass opacities with septal thickening giving the crazy-paving appearance. Studies for infections, vasculitis, Alpha-1 antitrypsin, hematologic malignancies, and myelodysplasia were all non-conclusive. PFT showed severe restriction and severe reduction in DLCO. She underwent bronchoscopy with a large volume lavage, which was positive for periodic acid-Schiff. She had a prolonged hospital course in ICU post treatment requiring using extracorporeal membrane oxygenation (ECMO) and tracheostomy. Rituximab was started and she improved partially on a follow up Computed tomography (CT) scan of the chest and PFT. Three months post treatment; she had a recurrence of her symptoms with another complicated course that was later treated with subcutaneous GM-CSF, which resulted in dramatic improvement in her respiratory status. A follow up Chest High Resolution CT scan showed further improvement in the diffuse lung ground glass density.
Discussion:
PAP is a rare disease attributed to an accumulation of large amounts of phospholipid/proteinaceous materials in the alveoli. There are three types; the first is congenital, due to mutations in surfactant proteins or to the GM-CSF receptor. The second is acquired, due to abnormal alveolar macrophage function in malignancies, infections, systemic inflammatory disorders, immunosuppression or toxic exposures. Finally, idiopathic, which is the most common and it is due to anti-GM-CSF antibodies inhibiting alveolar macrophage function,. A PFT demonstrates restrictive patterns with a decrease DLCO. Chest CT findings are ground-glass density with interlobular septal thickening giving the crazy-paving appearance. Serum anti-GM-CSF antibody titers or PAS positive BAL are helpful in the diagnosis. The treatment starts with a whole lung lavage (WLL), which is mostly curative for an acquired form of the disease. Autoimmune forms may respond to Rituximab, while another option is GM-CSF. Our patient failed the WLL, which supported diagnosis of an idiopathic cause and had a good response to recombinant GM-CSF.
Conclusion:
PAP has variable etiologies; although this is uncommon cause of diffuse parenchymal lung disease with crazy-paving appearance, the possibility of this disease should be considered.